Ionic Liquids for protein crystallization? Honestly, I don't get it.
Ionic liquids are a big topic in green chemistry since they provide solvents with a wealth of physical chemical behavior. What are ionic liquids?
Here's a hands-on primer on the topic of ionic liquids.
Think of a neat solution that consists of ions only and that is a fluid at room temperature. Take as a cation an organic compound and an another organic molecule as an anion. Typically these liquids are viscuous, transparent, have a low vapor pressure and are great solvents.
For a few years now, several researchers have employed ionic liquids as additives to promote protein crystallization. Here's a collection on papers on this topic:
Xinxin Li, Xiaodong Xu, Yuanyuan Dan, Jing Feng, Lan Ge, and Milin Zhang
The crystallization of lysozyme in the system of ionic liquid
[BMIm][BF4]-water
Cryst. Res. Technol. 43, No. 10, 1062 - 1068 (2008)
Russell A. Judge, Sumiko Takahashi, Kenton L. Longenecker, Elizabeth H. Fry, Cele Abad-Zapatero and Mark L. Chiu
The Effect of Ionic Liquids on Protein Crystallization and X-ray Diffraction Resolution
Cryst. Growth Des., 2009, 9 (8), pp 3463-3469
Dariusch Hekmat , Dirk Hebel, Sebastian Joswig, Michael Schmidt and Dirk Weuster-Botz
Advanced protein crystallization using water-soluble ionic liquids as crystallization additives
Biotechnol Lett (2007) 29: 1703-1711
And of course:
Pusey, M. L.; Paley, M. S.; Turner, M. B.; Rogers, R. D.
Protein Crystallization Using Room Temperature Ionic Liquids.
Cryst. Growth Des. 7, 787-793 (2007).
An example for an ionic liquid employed in protein crystallization is tri-isobutyl(methyl) phosphonium p-toluenesulfonate, also known as Triisobutylmethylphosphonium tosyylate.
One of the Ionic Liquids used by Judge et al. 2009, for the crystallization of the six model proteins lysozyme, catalase, myoglobin, trypsin, glucose isomerase, and xylanase. Shown is tri-isobutyl(methyl) phosphonium p-toluenesulfonate, also known as Triisobutylmethylphosphonium tosyylate, which forms a liquid at room temperature and is soluble inwater. This ionic liquid yields glucose isomerase crystals with changed morphology when present in the crystallization cocktail as a max 5% additive with the reservoir solution consisting of 1.6 M ammonium sulfate, 0.1 M Tris-
HCl pH 8.0.
The reports referenced above describe dramatic effects of ionic liquids when they are added to the aqueous solutions that the protein crystallizations are carried out in. The ionic liquids are described either as crystallization inducing agents or as crystallization additives.
Here's what I don't get: Once the ions dissociate and dissolve in water they're no different from ions that are brought in as solid salts - right? I understand that the inorganic counter ions are absent with ionic liquids in water, but check out the crystallization cocktails. There is plenty of salt and pH'ed buffer around. Lot's of inorganic cations and anions. Since the organic compounds appear to effect protein crystallization, why not bring them in as salts in the first place? What's the difference that is responsible for the effects seen in the reported cases of altering protein crystallization behavior?
Please enlighten me!
Peter